基于网络药理学分析贾跃进老师膏方调治慢性失眠经验

Jia Yuejin′s Experience in Treating Chronic Insomnia with Paste Recipe Based on Network Pharmacology

目的通过联合理论分析、数据挖掘及网络药理学方法,全面探究贾跃进老师临床膏方调治慢性失眠与治疗经验。方法首先对贾跃进老师膏方调治慢性失眠的思路进行分析,其次使用古今医案云平台V2.2.3将贾跃进老师门诊近5年膏方调治慢性失眠的处方进行药物频次、属性统计以及关联、聚类和复杂网络分析,得出核心组方。再将核心组方运用中药系统药理学数据库与分析平台(TCMSP)、Gene Expression Omnibus数据库(GEO)等数据库得到各药物有效成分的靶点与疾病靶点并取交集,利用CytoscapeV 3.8.0及其插件构建疾病-药物-成分-靶点与蛋白互作网络并进行基因本体(GO)和京都基因和基因组百科全书(KEGG)通路富集分析,最后选取关键有效成分和关键靶点,应用Vina分子对接。结果数据挖掘获得病案122个、方剂138首,涉及中药154味;药性以平、温为多;药味以甘、辛、苦为主;药物主要归脾、肝经;通过药物关联、聚类和复杂网络分析综合得出9味药物的核心组方。共获得核心组方有效成分72种,相关靶点476个,交集基因116个,关键成分有α-香树素、豆甾醇等,关键靶点有AKT1、NTRK1等。GO功能富集分析结果主要有生物调节、信号通路等;KEGG通路富集分析结果主要有神经活性配体-受体相互作用、血清素能突触等;关键成分和关键靶点分子对接显示其多可形成稳定结合。结论初步得出贾跃进老师膏方调治慢性失眠的经验认识、用药规律及其相关多成分、多靶点、多通路作用机制,为临床使用和进一步研究提供参考。

Objective Through the combination of theoretical analysis,data mining and network pharmacology methods,to explore the experiences of Jia Yuejin′s clinical paste prescription in treating chronic insomnia.Methods Firstly,the thought of Jia Yuejin′s prescription for treating chronic insomnia was analyzed.Secondly,the ancient and modern medical record cloud platform V2.2.3 was used to analyze the prescription of Jia Yuejin′s prescription for treating chronic insomnia in the past five years,including drug frequency,attribute statistics,association,clustering,and complex network analysis,to obtain the core prescription.Then,the core formulae were used to obtain the targets and disease targets of the active components of each drug using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP),Gene Expression Omnibus database(GEO)and other databases,and the intersection was taken.CytoscapeV 3.8.0 and its plug-ins were used to construct disease-drug-component-target and protein-protein interaction networks and performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,the key active components and key targets were selected,and Vina software was used for molecular docking.Results Data mining obtained 122 medical records,138 prescriptions,involving 154 flavors of traditional Chinese medicine.The most common drug properties were gentle and warm.The main taste of the medicine was sweet,pungent and bitter.The meridian were mainly concentrated in spleen and liver.Through drug association,clustering and complex network analysis,the core formulae of 9 drugs were obtained.A total of 72 active components,476 related targets and 116 intersection genes were obtained from the core formula.The key components includedα-amyrin and stigmasterol,and the key targets included AKT1 and NTRK1.GO functional enrichment analysis results mainly included biological regulation,signaling pathway,etc.KEGG pathway enrichment analysis results mainly included neuroactive ligand-receptor interaction,serotonergic synapses,etc.Molecular docking of key components and key targets showed that most of them could form stable binding.Conclusion In this study,the empirical understanding,medication rules and related multi-component,multi-target and multi-pathway mechanism of Jia Yuejin′s paste recipe in the treatment of chronic insomnia were obtained,which could provide reference for clinical use and further research.